Silicosis is an occupational lung disease resulting from the inhalation of silica particles which causes chronic inflammation and progressive pulmonary fibrosis. Phagocytosis of inhaled silica particles by alveolar macrophages (AM) and subsequent activation of AM is a crucial step in the pathogenesis of silicosis; however, the participation of specific intracellular signaling pathways in regulating this process remains largely unknown. The goal of this study is to test the central hypothesis that silica induced production of TNF alpha sustains inflammation by activating the Akt signaling pathway in AM. The specific aims of this proposed research are: 1) to assess the cellular fate of AM following exposure to silica, 2) to determine the effects of silica on the Akt signaling pathways in AM, and 3) to elucidate the ability of silica induced TNF alpha production to stimulate the Akt signaling pathway and alter call fate (apoptosis vs. survival). Defining the function of this signaling pathway in regulating AM activation and cell fate is of interest because a better understanding of the molecular events involved may permit targeting of key biochemical pathways for more effective diagnosis and treatment of occupational lung diseases.